P1022: OUTCOMES IN MYELOPROLIFERATIVE NEOPLASM PATIENTS WITH OR WITHOUT PRIOR HISTORY OF CANCER: A POPULATION-BASED STUDY FROM ONTARIO
Authors: J. T. England, A. Bankar, W. C. Chan, N. Liu, M. C. Cheung, V. Gupta
Journal: HemaSphere (2022)

Background: Therapy-related myeloid neoplasms (tMNs) exist as a distinct diagnostic entity in the 2016 WHO classification, and include MDS, MDS/MPN overlap, and AML that develop following iatrogenic exposure to mutagenic agents and ionizing radiation. Patients with the classical myeloproliferative neoplasms (MPNs), essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF), are excluded from the tMN category. Prior studies have observed an increased risk of other cancers in patients with MPNs, possibly from shared risk factors including older age and chronic inflammation. The impact of prior history of cancer on outcomes in MPN patients is not well understood. A single centre study of MF (Masarova et al, Blood Advances, 2017) found no survival difference between patients exposed to chemotherapy/radiation and those managed with surgery/observation/hormone therapy. Aims: To evaluate the clinical outcomes of MPN patients with or without prior non-MPN cancer, and the impact of tMN-implicated therapy on survival following MPN diagnosis. Methods: We conducted a population-based, retrospective cohort study using the ICES provincial health databases. Included patients were residents of Ontario aged ≥18 years with an MPN diagnosis from Jan 1, 2004 to Dec 31, 2019. Diagnoses of MPN and non-MPN (other cancers excluding AML) cancers were based on International Classification of Diseases for Oncology, third edition (ICD-O-3) codes. Therapy for prior non-MPN cancer were grouped as: therapy implicated in tMN per 2016 WHO criteria (alkylating agents, antimetabolites, topoisomerase inhibitors, antitubulin agents, and ionizing radiation), non-implicated therapies (targeted inhibitors, hormone therapy, other), and surgery/observation alone. The primary outcome was overall survival (OS) from the MPN diagnosis, with multivariable Cox regression adjusted for age and comorbidities. In addition, to understand the patterns of non-MPN cancer type, therapy exposure, and latency period, we compared the MPN cohort with a control cohort with no MPN history matched (1:4) for age (±3 years), gender, geographic location, and neighbourhood income quintile. Results: A total of 10 336 MPN patients (5108 ET, 3843 PV, and 1385 MF) matched to 41 344 controls were identified in the study. MPN patients more frequently had a history of non-MPN cancer compared to the control cohort (n=1421[13.5%] vs. n=5509[11.9%], P<0.001). The most common non-MPN cancers were male genitourinary (24%), breast (18%), gastrointestinal (18%), urothelial (9%), and melanoma (5%). Comparing MPN patients to matched controls, there was no difference in the types of non-MPN cancer, treatment exposures, or latency time. After adjustment for age and comorbid conditions, the OS from PV/ET diagnosis was predicted by prior cancer managed with surgery/observation hazard ratio (HR)[95% confidence interval] 1.36 [1.22-1.52], tMN-implicated therapy HR1.83 [1.55-2.18] and non-implicated therapy HR1.88 [1.49-2.38] (Fig 1a). In MF patients the OS was predicted by tMN therapy, HR1.44 [1.04-1.98]; but not surgery/observation, HR1.17 [0.94-1.46], or non-implicated therapy, HR1.25 [0.83-1.87](Fig 1b). Lack of availability of cytogenetics and mutation profile in this population based dataset is the main limitation of this study. Image:Summary/Conclusion: Compared with matched controls, patients with MPNs are more likely to have had a history of prior cancer. MPN patients with prior cancer have worse OS; and those treated with systemic therapies have shorter OS than patients managed with surgery/observation alone.